Intrauterine exposure to ethanol is associated with retardation of brain and somatic growth resulting in permanent growth deficiency and mental retardation. These featues of the fetal alcohol syndrome have been replicated in the rat and other laboratory animals. Studies with the rat indicate that maternal growth hormone (GH) plays an important role in maintaining normal fetal development particularly in the compromised pregnancy. Since preliminry studies by the applicant indicate that ethanol blocks GH secretion it appears likely that suppression of maternal GH secretion may be a critical event in the pathogenesis of the fetal alcohol syndrome. In addition, other endocrine aberations produced by ethanol, specifically lower levels of thyroxine (T4) and triiododothyronine T3 and elevated levels of corticosterone (CS) may adversely impair maternal ability to support fetal growth and development. It is proposed to test these hypotheses with the following series of experiments: (1) determine the dose-responde relationship of chronic ethanol treatment to decrease weight, length and brain cellularity of the offspring in the rat, (2) utilize a nonstressful frequent sampling method to define the dose-response relationship for inhibition of GH secretion in pregnant rats, (3) seek altered levels of T4, T3 and CS in these rats, and (4) determine the extent to which administration of GH to the mother protects the fetus against the effects of maternal ethanol. Achievement of these specific aims would help to: (1) establish causality in the ethanol-birth defects association, (2) understand the alterations in the physiology of pregnancy produced by ethanol, (3) quantitate the relationship between ethanol dose and abnormal fetal development, and (4) suggest possible therapeutic interventions.